[go: up one dir, main page]

WO2017181977A1 - Mussel adhesive protein product and use thereof for inhibiting soft tissue inflammation - Google Patents

Mussel adhesive protein product and use thereof for inhibiting soft tissue inflammation Download PDF

Info

Publication number
WO2017181977A1
WO2017181977A1 PCT/CN2017/081307 CN2017081307W WO2017181977A1 WO 2017181977 A1 WO2017181977 A1 WO 2017181977A1 CN 2017081307 W CN2017081307 W CN 2017081307W WO 2017181977 A1 WO2017181977 A1 WO 2017181977A1
Authority
WO
WIPO (PCT)
Prior art keywords
mussel mucin
soft tissue
mussel
tissue inflammation
mucin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2017/081307
Other languages
French (fr)
Chinese (zh)
Inventor
高敏
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bengt I Samuelsson Institute Of Life Science Co Ltd
Original Assignee
Bengt I Samuelsson Institute Of Life Science Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bengt I Samuelsson Institute Of Life Science Co Ltd filed Critical Bengt I Samuelsson Institute Of Life Science Co Ltd
Publication of WO2017181977A1 publication Critical patent/WO2017181977A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/12Aerosols; Foams

Definitions

  • the present invention relates generally to the fields of pharmaceuticals, medical products, health care products, and food technology, and more particularly to mussel mucin products and their use in inhibiting inflammation of soft tissues.
  • Soft tissue refers to the subcutaneous tissue, muscle, tendon, ligament, joint capsule and other tissues of the human body.
  • Soft tissue inflammation refers to a large class of microcirculatory disorders and aseptic inflammation caused by direct or indirect violence or long-term chronic strain of soft tissue.
  • causes of soft tissue inflammation include knives, falls, beatings, contusions, puncture wounds, abrasions, sports injuries, etc.
  • the clinical manifestations are mainly swelling and pain. Local oozing, edema, and severe pain in the acute phase. In the late stage, muscle, tendon adhesion, ischemic contracture, inflammation around the joints, and even joint stiffness may occur.
  • Soft tissue inflammation treatment usually chooses different methods according to different degrees. Mild inflammation often uses physical therapy such as cold compress, hot compress and massage.
  • Severe inflammation is often treated with non-steroidal anti-inflammatory drugs.
  • drugs include aspirin, acetaminophen, indomethacin, naproxen, naproxen, diclofenac, ibuprofen, nimesulide, rofecoxib, celecoxib, etc., mainly through inhibition
  • the synthesis of prostaglandins exerts its anti-inflammatory, anti-rheumatic, analgesic, antipyretic and anticoagulant effects.
  • FDA US Food and Drug Administration
  • Mussel adhesive protein also known as Mytilus edulis foot protein (Mefp)
  • Mefp Mytilus edulis foot protein
  • Mytilus coruscus A special protein secreted by Perna viridis. Mussels are usually attached in groups to the reefs on the coast or to the bottom of the ship, and have the ability to withstand wave impacts in the offshore. In fact, mussels can be attached extremely strongly to the substrate of any material, such as metal, wood, glass, and the like. The main reason for the above characteristics of mussels is that they can produce and store this special mucin in the girth of the foot, and the mussels are released through the foot. Mucin forms a water-resistant bond to a solid surface such as rock, thereby fixing itself.
  • Mussel mucin has two structural features: (1) containing lysine, which has a high loading of positive charge; (2) containing 3,4 dihydroxyphenylalanine (DOPA, dopa). The cells and tissues of the human body are negatively charged.
  • Mussel mucin plays a protective and therapeutic role by tightly binding cells and tissues through the electrostatic interaction between its own positive charge and the negative charge of cells and tissues.
  • dopa oxidation produces ortho-dioxins, which can be cross-linked with unoxidized dopa to form a membrane or a network scaffold, which promotes the protein to adhere more closely and firmly to the surface of the human body, thereby protecting.
  • Mussel mucin is a macromolecular protein that is completely degraded in the human body for about 3-10 days. Its ability to attach to cell tissues is excellent, so that mussel mucin can be stabilized locally and continue to function.
  • mussel mucin has the above characteristics, its current application field is very limited.
  • Commercial mussel mucin products are Cell-Tak from BD Biosciences, MAP Trix from Kollodis, Korea, and Hydrogel from Biopolymer, Sweden. These products are either used directly in the mussel mucin solution state, or are stored as lyophilized powder formulations and dissolved prior to use. Their primary application is limited to microscopic cell adhesion and tissue adhesives. Mussel mucin has also been reported for use in the repair of fetal membranes, as a coating against seawater corrosion, and as a drug-loaded stent for the heart.
  • Mussel mucin used herein refers to Mytilus edulis Linnaeus, Mytilus coruscus or Perna viridis from the Mytilidae bivalve mollusc. 11 subclasses of mussel mucin, currently known as purified from marine mussels: mefp1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, collagen pre-COL- A mixture of one or more of P, pre-COL-D, pre-COL-NG, foot silk matrix proteins PTMP and DTMP.
  • the mussel mucin used herein may have a pH of 1.0 to 7.0 in an aqueous solution, and particularly may be in the range of pH 3.0 to 6.5 to make the therapeutic effect better.
  • the mussel mucin used herein can be obtained by the following preparation methods, such as Chinese A method for separating and purifying mussel mucin using mixed adsorption chromatography, ZL200710179491.0, Chinese Patent No. ZL200710179492.5, a method for purifying mussel mucin using carboxymethyl ion exchange chromatography, Chinese Patent No. ZL200910087567.
  • the mussel mucin used herein may be in the form of a solution or a lyophilized powder, in particular, the concentration of mussel mucin in the product may be 0.1-15.0 mg/ml, and when the concentration is too low, the effect of mussel mucin Not large, when the concentration is too high, it can cause cytotoxicity, skin irritation, etc., which is not conducive to the treatment of soft tissue inflammation.
  • the mussel mucin used herein can also be prepared as a liquid agent by combining it with an excipient.
  • An exemplary mussel mucin liquid preparation is prepared by dissolving or diluting mussel mucin solution mother liquor or lyophilized powder to a certain concentration or pH, and the solution for dissolving or diluting may be water, physiological saline, phosphate solution, vinegar. Acid solution, borate solution, and the like.
  • the pH of mussel mucin in the final product may be pH 1.0-7.0, and in particular, the therapeutic effect may be better in the range of pH 3.0-6.5.
  • the mussel mucin used herein can also be prepared as a gelling agent in combination with an excipient.
  • An exemplary mussel mucin gel is prepared by mixing a mussel mucin solution or a lyophilized powder with a gel matrix material, which may be selected from the group consisting of cellulose derivatives, carbomers, and seaweeds. Acid salt, tragacanth, gelatin, pectin, carrageenan, gellan gum, starch, xanthan gum, cationic guar gum, agar, non-cellulosic polysaccharide, ethylene polymer, acrylic resin, polyvinyl alcohol or poly One of carboxyvinyl or any combination thereof.
  • the mussel mucin used herein can be used as a main raw material to prepare a medicine using a pharmaceutically acceptable carrier.
  • the drug may be a liquid agent or a gel.
  • the drug may be administered by oral, spray, injection, targeted topical sustained release, targeted administration, and may be administered at a low temperature or in a heated manner.
  • the mussel mucin used herein can be used as a main raw material to prepare a medical device.
  • the term medical device as used herein refers to materials that are used directly or indirectly to the human body and other similar or related items.
  • the medical device may be a liquid agent, a gel, or a foaming agent.
  • the medical device can It is used by oral administration, spraying, injection, targeted local sustained release, targeted administration, and can be administered at a low temperature or in a heated manner.
  • the mussel mucin used herein can be used as a main raw material, and a health care product or food can be prepared by using an excipient which is acceptable in the field of health care or food.
  • the health care product or food may be a liquid agent or a gel.
  • the health supplement or food may be administered by oral, spray, injection, targeted topical sustained release, targeted administration, and may be administered at a low temperature or in a heated manner.
  • Another object of the invention is to provide the use of mussel mucin products to inhibit soft tissue inflammation.
  • mussel mucin can alleviate various soft tissue inflammations such as muscles, ligaments, fascia, tendons, synovial membranes, fat, joint capsules, and contusions or lacerations of lymphoid tissues.
  • Musitis refers to chronic inflammation of muscles or tendons and attachments or tendon sheaths due to chronic damage, wind and cold dampness, infection, muscle spasms and other factors.
  • Ligamentitis is a chronic, non-red, non-swelling, non-fever, painful aseptic inflammatory injury.
  • the treatment of ligamentitis is based on physiotherapy, supplemented by non-steroidal anti-inflammatory drugs such as fenbide.
  • Fasciitis is a non-specific inflammation that occurs in the myofascial fascia. Can occur in all parts of the body, more common in the waist, the posterior tibial and the scapular region.
  • Non-steroidal anti-inflammatory drugs such as ibuprofen and diclofenac are commonly used drugs for the treatment of fasciitis.
  • Tendinitis refers to the degenerative pathological changes of tendon collagen fibers caused by excessive use of muscle fibers and repeated intense pulling. In addition to involving the tendon itself, it can also involve the tendon sheath. In most cases, it is often associated with the degeneration of collagen tissue in the affected tendon, so it is now known as tendinopathy. Tendinitis uses non-steroidal anti-inflammatory drugs to relieve pain, severe pain, and local injection of steroids. However, multiple injections of steroids weaken the strength of the tendon and cause the tendon to break.
  • Synovitis is a form of aseptic inflammation caused by joint sprains and multiple intra-articular injuries. Abnormal function of the synovial membrane can cause the joint fluid to fail to form and absorb normally, and the joint will produce fluid accumulation. The morphological changes of the synovial membrane can also invade the articular cartilage. If it is not treated in time, it will lead to osteoarthritis of the joints, and there is a disability crisis.
  • Lipitis is inflammation caused by damage to connective tissue between the lobule and the lobule composed of subcutaneous fat cells.
  • the clinical manifestations lack specificity.
  • the subcutaneous nodules or plaques are light red to tan, and the size and number are uncertain, and the pain and tenderness are conscious.
  • Joint capsule inflammation is an acute or chronic inflammation of the joint capsule. It is caused by direct violent injury, joint flexion, extension, abduction, external rotation, etc., caused by repeated, long-term, continuous friction and compression. disease. Clinical manifestations include pain, localized tenderness, limited mobility, and swelling.
  • the treatment of joint capsule is treated with rest or affected part of the brakes and high-dose non-steroidal anti-inflammatory drugs, if necessary, anesthesia sedatives.
  • Lymphadenitis is a non-specific inflammation caused by acute and chronic inflammation involving lymph nodes in the drainage area of the lymph nodes.
  • the infection of the upper limbs, breast, chest wall, back and ventral wall of the umbilicus causes axillary lymphadenitis; lower limbs, abdominal wall below the umbilicus, perineum Infections in the buttocks can occur in the inguinal lymphadenitis; infections in the head, face, mouth, neck and shoulders cause lymphadenitis in the submandibular and neck.
  • mussel mucin can be used to treat soft tissue inflammation caused by contusions or lacerations of muscles, ligaments, fascia, tendons, synovial membranes, fat, joint capsules, lymphoid tissues, and the like.
  • the mussel mucin of the present invention can be used externally, directly acts on the affected part by transdermal absorption, and can also be absorbed to exert an anti-inflammatory pharmacological action.
  • mussel mucin as a broad-spectrum anti-inflammatory agent does not cause damage to other tissues or organs.
  • Fig. 1 shows a mussel mucin liquid medicine of the present invention for use in treatment of muscle tissue inflammation, the upper graph being the day of treatment on day 0, and the lower panel being the result on day 21.
  • the mussel mucin application according to embodiment 1, wherein the mussel mucin concentration may be from 0.1 to 15.0 mg/ml.
  • Mussel mucin application according to embodiment 1, wherein the mussel mucin in the final product may be in the range of pH 1.0-7.0, in particular in the range of pH 3.0-6.5.
  • the mussel mucin application according to any one of embodiments 1 to 5, wherein the soft tissue inflammation
  • the disease can be selected from the group consisting of: muscle, ligament, fascia, tendon, synovium, fat, joint capsule, lymphoid tissue contusion or laceration caused by soft tissue inflammation.
  • composition can be used by oral, spray, injection, targeted local sustained release, targeted administration.
  • a medicament for the treatment of soft tissue inflammation comprising mussel mucin and a pharmaceutically acceptable carrier, wherein the mussel mucin is present in a concentration of from 0.1 to 15.0 mg/ml.
  • a medical device for treating inflammation of a soft tissue comprising a mussel mucin and a carrier acceptable for use in the field of medical devices, wherein the concentration of mussel mucin may be from 0.1 to 15.0 mg/ml.
  • a health supplement/food for treating soft tissue inflammation comprising mussel mucin and a health care product or a carrier acceptable for the food field, wherein the mussel mucin concentration may be from 0.1 to 15.0 mg/ml.
  • soft tissue inflammation may be selected from the group consisting of muscles, ligaments, fascia, tendons, synovium, fat, joint capsule, and contusion or crack of lymphoid tissue. Soft tissue inflammation caused by injury.
  • the use of mussel mucin in a health care product or food for treating soft tissue inflammation wherein the soft tissue inflammation can be selected from the group consisting of: muscle, ligament, fascia, tendon, synovium, fat, joint capsule, lymphoid tissue. Soft tissue inflammation caused by contusion or laceration.
  • a method of treating inflammation of a soft tissue comprising formulating a mussel mucoid liquid or gel according to any one of the preceding embodiments 10-12 and administering to a subject in need thereof, wherein mussel mucin
  • the concentration can be from 0.1 to 15.0 mg/ml.
  • the soft tissue inflammation is selected from the group consisting of: muscle, ligament, fascia, tendon, synovial membrane, fat, joint capsule, contusion of a lymphoid tissue or soft tissue inflammation caused by a laceration.
  • Example 1 Application of mussel mucin gel drug in the treatment of leg muscle injury.
  • the mussel mucin solution was taken, mixed with guar gum and glycerol at a volume ratio of 2:1:1, and water was added thereto, and the pH was adjusted to 3.0 with citric acid to prepare a mussel mucoprotein content of 1.5 mg/ml.
  • Shell mucin gel drug was taken, mixed with guar gum and glycerol at a volume ratio of 2:1:1, and water was added thereto, and the pH was adjusted to 3.0 with citric acid to prepare a mussel mucoprotein content of 1.5 mg/ml.
  • Shell mucin gel drug was taken, mixed with guar gum and glycerol at a volume ratio of 2:1:1, and water was added thereto, and the pH was adjusted to 3.0 with citric acid to prepare a mussel mucoprotein content of 1.5 mg/ml.
  • Shell mucin gel drug was taken, mixed with guar gum and glycerol at a volume ratio of 2:1:1, and water was added thereto, and the pH was adjusted to 3.0
  • the clinical manifestations of the selected cases were pain, swelling, tenderness or spasm.
  • the selected cases were randomly assigned to the control group or the experimental group.
  • the control group was treated with Yunnan Baiyao aerosol for 2 times a day.
  • the dosage should be able to cover the affected area evenly.
  • the test group used mussel mucin gel drug to spread the affected area. Second, the dosage should be able to cover the affected area evenly. There was no significant change in the control group after administration.
  • the pain in the affected area was significantly weakened in the test group within 10-30 minutes.
  • the visual analog VAS score decreased from 4.0-6.0 to 1.0-3.0 before treatment, and the analgesic time lasted for 2-5 hours. Also, as the use interval is extended, no dependence is exhibited.
  • Example 2 Application of mussel mucin liquid medical device in the treatment of ankle ligament injury.
  • a mussel mucin solution having a concentration of 0.5 mg/ml was prepared, diluted 5 times with 0.001% acetic acid, and the mussel mucin content was 0.1 mg/ml to obtain a mussel mucin liquid medical device.
  • the selected cases were randomly assigned to the control group or the experimental group.
  • the control group was treated with Yunnan Baiyao aerosol for 3 times a day.
  • the dosage should be able to cover the affected area evenly.
  • the selected cases were sprayed with mussel mucin liquid medicine for 3 times a day.
  • the dosage should be able to cover the affected area evenly.
  • the pain in the control group was not relieved.
  • the pain in the affected area was significantly weakened in the test group within 20-40 minutes.
  • the visual analog VAS score was 4.0-6.0 before treatment to 1.0-3.0, and the analgesic time lasted 2-5 hours. Also, as the use interval is extended, no dependence is exhibited.
  • Example 3 Application of mussel mucin liquid medicine in the treatment of fasciitis.
  • a mussel mucin solution having a concentration of 10.0 mg/ml was diluted with 0.01% citric acid to a mussel mucin content of 1.0 mg/ml to obtain a mussel mucin liquid medicine.
  • Example 4 Application of mussel mucin gel medical device in the treatment of tendon injury.
  • Example 5 Application of mussel mucin gel medical device in the treatment of knee joint synovitis.
  • Example 6 Application of mussel mucin liquid medicine in the treatment of tonsillitis.
  • a mussel mucin solution having a concentration of 10.0 mg/ml was diluted with 0.01% citric acid to a mussel mucin content of 0.5 mg/ml to obtain a mussel mucin liquid medicine.
  • Ten patients with acute tonsillitis diagnosed by otolaryngologists were collected. The clinical manifestations of the patients were systemic fever and sore throat. The selected cases were randomly assigned to the control group or the experimental group. The control group was treated with oral penicillin twice a day. The test group was treated with mussel mucin liquid medicine and sprayed on the throat 3 times a day. . After 2 days of treatment, the fever symptoms of the control group disappeared and the sore throat was relieved; the fever symptoms disappeared and the sore throat was relieved in the test group. After 4 days of treatment, all the patients in the control group and the test group had normal body temperature and the symptoms of sore throat disappeared. It can be seen that mussel mucin liquid medicine can be used for the treatment of tonsillitis.
  • Example 7 Application of mussel mucin liquid medicine in the treatment of chronic refractory inflammatory wounds
  • the mussel mucin solution (MAP) was prepared by column chromatography with a protein concentration of 5.0 mg/ml and a purity of 90%. The above mussel mucin solution was taken and diluted with physiological saline to a mussel mucin content of 0.5 mg/ml to obtain a mussel mucin liquid medicine. Each 100 ml mussel mucin product contains mussel mucin 0.5 mg, sodium chloride 0.9 g, and the rest is water for injection.
  • the selected cases were randomly assigned to the control group or the experimental group.
  • the control group was treated with the original succulent muscle cream (Jie Chuang, Wei Shi Tai Tang Tang Pharmaceutical) twice a day.
  • the test group was treated with mussel mucin liquid medicine. 2 times a day. After 21 days of treatment, the chronic wounds of 6 patients in the control group showed no significant improvement. In the experimental group, 3 of the 6 patients basically healed, and the other 3 patients achieved a healing rate of more than 90%.
  • Mussel mucin liquid medicine can be used for the treatment of chronic refractory inflammatory wounds and can be used to repair damaged muscle tissue.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dispersion Chemistry (AREA)
  • Birds (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)

Abstract

Disclosed in the present invention is a use of a mussel adhesive protein or a preparation thereof for inhibiting soft tissue inflammation. Specifically disclosed is the use of the mussel adhesive protein or preparation thereof in the treatment of soft tissue inflammation and the like caused by contusion or laceration of muscle, ligament, fascia, tendon, synovial membrane, fat, joint capsule and lymphatic tissue. The mussel adhesive protein or preparation thereof can inhibit the redness, swelling, hotness, pain and other symptoms caused by soft tissue inflammation.

Description

贻贝粘蛋白产品及其抑制软组织炎症的应用Mussel mucin product and its application for inhibiting soft tissue inflammation

本申请要求于2016年04月20日提交中国专利局的申请号为PCT/CN2016/079768、名称为“贻贝粘蛋白产品及其抑制软组织炎症的应用”的国际专利申请的优先权,其全部内容通过引用结合在本申请中。This application claims priority to the International Patent Application No. PCT/CN2016/079768, entitled "Mub Shell Mucin Product and Its Application for Inhibiting Soft Tissue Inflammation", filed on April 20, 2016, all of which is hereby incorporated by reference. The content is incorporated herein by reference.

技术领域Technical field

本发明大体涉及药品、医疗产品、保健品及食品技术领域,更具体地,涉及贻贝粘蛋白产品及其在抑制软组织炎症中的应用。The present invention relates generally to the fields of pharmaceuticals, medical products, health care products, and food technology, and more particularly to mussel mucin products and their use in inhibiting inflammation of soft tissues.

相关技术讨论Related technical discussion

软组织是指人体的皮下组织、肌肉、肌腱、韧带、关节囊等组织,软组织炎症是指软组织受到直接或间接暴力,或长期慢性劳损引起的一大类微循环障碍、无菌性炎症等。造成软组织炎症的原因包括刀枪、摔伤、殴打、挫伤、穿刺伤、擦伤、运动损伤等。临床表现以肿胀、疼痛为主。急性期局部渗血、水肿,疼痛剧烈。晚期可能出现肌肉、肌腱的粘连、缺血性挛缩,关节周围炎,甚至引起关节僵直。软组织炎症治疗通常根据程度不同选择不同的方法,轻度炎症常采用冷敷、热敷、推拿等物理疗法,重度炎症常采用非甾体抗炎药物治疗。这类药物包括阿司匹林、对乙酰氨基酚、吲哚美辛、萘普生、萘普酮、双氯芬酸、布洛芬、尼美舒利、罗非昔布、塞来昔布等,主要是通过抑制前列腺素的合成发挥其抗炎、抗风湿、止痛、退热和抗凝血等作用。最近美国食品药品监督管理局(FDA)认为非甾体抗炎药物存在潜在的心血管和消化道出血风险,同时可引起不程度的胃肠道、肝脏、神经系统、泌尿系统等不良反应。Soft tissue refers to the subcutaneous tissue, muscle, tendon, ligament, joint capsule and other tissues of the human body. Soft tissue inflammation refers to a large class of microcirculatory disorders and aseptic inflammation caused by direct or indirect violence or long-term chronic strain of soft tissue. Causes of soft tissue inflammation include knives, falls, beatings, contusions, puncture wounds, abrasions, sports injuries, etc. The clinical manifestations are mainly swelling and pain. Local oozing, edema, and severe pain in the acute phase. In the late stage, muscle, tendon adhesion, ischemic contracture, inflammation around the joints, and even joint stiffness may occur. Soft tissue inflammation treatment usually chooses different methods according to different degrees. Mild inflammation often uses physical therapy such as cold compress, hot compress and massage. Severe inflammation is often treated with non-steroidal anti-inflammatory drugs. Such drugs include aspirin, acetaminophen, indomethacin, naproxen, naproxen, diclofenac, ibuprofen, nimesulide, rofecoxib, celecoxib, etc., mainly through inhibition The synthesis of prostaglandins exerts its anti-inflammatory, anti-rheumatic, analgesic, antipyretic and anticoagulant effects. Recently, the US Food and Drug Administration (FDA) believes that non-steroidal anti-inflammatory drugs have potential cardiovascular and gastrointestinal bleeding risks, and can cause adverse reactions such as gastrointestinal, liver, nervous system, and urinary system.

贻贝粘蛋白(Mussel adhesive protein,MAP),也称作贻贝足丝蛋白(Mytilus edulis foot protein,Mefp),是海洋贝类紫贻贝(Mytilus edulis Linnaeus)、厚壳贻贝(Mytilus coruscus)、翡翠贻贝(Perna viridis)等分泌的一种特殊的蛋白质。贻贝通常成群地附着在海岸边的礁石上或者轮船的底部,有在近海耐受波浪冲击的能力。实际上贻贝几乎可以极其牢固地附着在任何材料的基底上,如金属、木材、玻璃等。贻贝具有上述特性的主要原因是其足丝腺内可生成并储存这种特殊的粘蛋白,贻贝通过足丝释放 粘蛋白到岩石一类的固体表面上,形成抗水的结合,从而将自己固定。Mussel adhesive protein (MAP), also known as Mytilus edulis foot protein (Mefp), is a marine shellfish, Mytilus edulis Linnaeus, and a small shell mussel (Mytilus coruscus). A special protein secreted by Perna viridis. Mussels are usually attached in groups to the reefs on the coast or to the bottom of the ship, and have the ability to withstand wave impacts in the offshore. In fact, mussels can be attached extremely strongly to the substrate of any material, such as metal, wood, glass, and the like. The main reason for the above characteristics of mussels is that they can produce and store this special mucin in the girth of the foot, and the mussels are released through the foot. Mucin forms a water-resistant bond to a solid surface such as rock, thereby fixing itself.

目前从贻贝中鉴定得到11种粘蛋白亚类,包括mefp1、mefp-2、mefp-3、mefp-4、mefp-5、mefp-6、胶原蛋白pre-COL-P、pre-COL-D、pre-COL-NG、足丝基质蛋白PTMP和DTMP(朱曜曜等,海洋科学进展,2014,32(4):560-568)。贻贝粘蛋白具有2个结构特点:(1)含有赖氨酸,使蛋白带有高载量正电荷;(2)含3,4二羟基苯丙氨酸(DOPA,多巴)。人体的细胞和组织带有负电荷。贻贝粘蛋白通过自身正电荷与人体的细胞和组织负电荷之间的静电相互作用与细胞和组织紧密结合,发挥防护和治疗的作用。此外,多巴氧化生成邻位二醌,可以和未被氧化的多巴相互交联形成膜或是网状支架,促使蛋白质更加紧密、稳固地附着在人体表面,起到保护作用。贻贝粘蛋白是大分子蛋白质,在人体内完全降解的时间约为3-10天,其附着于细胞组织的能力优异,使贻贝粘蛋白可以稳固于局部,持续发挥作用。Currently, 11 mucin subclasses have been identified from mussels, including mefp1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, collagen pre-COL-P, pre-COL-D. , pre-COL-NG, foot silk matrix proteins PTMP and DTMP (Zhu Xi et al, Advances in Marine Science, 2014, 32(4): 560-568). Mussel mucin has two structural features: (1) containing lysine, which has a high loading of positive charge; (2) containing 3,4 dihydroxyphenylalanine (DOPA, dopa). The cells and tissues of the human body are negatively charged. Mussel mucin plays a protective and therapeutic role by tightly binding cells and tissues through the electrostatic interaction between its own positive charge and the negative charge of cells and tissues. In addition, dopa oxidation produces ortho-dioxins, which can be cross-linked with unoxidized dopa to form a membrane or a network scaffold, which promotes the protein to adhere more closely and firmly to the surface of the human body, thereby protecting. Mussel mucin is a macromolecular protein that is completely degraded in the human body for about 3-10 days. Its ability to attach to cell tissues is excellent, so that mussel mucin can be stabilized locally and continue to function.

虽然贻贝粘蛋白具有以上特点,但目前其产品应用领域非常有限。商品化的贻贝粘蛋白产品有美国BD Biosciences的Cell-Tak,韩国Kollodis的MAP Trix和瑞典Biopolymer的Hydrogel。这些产品或者是以贻贝粘蛋白溶液状态直接使用,或者是以冻干粉制剂保存而在使用前溶解,它们的主要应用限于微观的细胞粘附和组织粘合剂。也有报道贻贝粘蛋白用于胎膜修复、作为抗海水腐蚀涂层、心脏载药支架等应用。Although mussel mucin has the above characteristics, its current application field is very limited. Commercial mussel mucin products are Cell-Tak from BD Biosciences, MAP Trix from Kollodis, Korea, and Hydrogel from Biopolymer, Sweden. These products are either used directly in the mussel mucin solution state, or are stored as lyophilized powder formulations and dissolved prior to use. Their primary application is limited to microscopic cell adhesion and tissue adhesives. Mussel mucin has also been reported for use in the repair of fetal membranes, as a coating against seawater corrosion, and as a drug-loaded stent for the heart.

发明内容Summary of the invention

本发明的一个目的是提供贻贝粘蛋白产品。It is an object of the present invention to provide a mussel mucin product.

在本文中使用的贻贝粘蛋白是指从贻贝科(Mytilidae)双壳类软体动物中的紫贻贝(Mytilus edulis Linnaeus)、厚壳贻贝(Mytilus coruscus)或翡翠贻贝(Perna viridis)等海洋贻贝中纯化获得的、目前已知的贻贝粘蛋白11个亚类:mefp1、mefp-2、mefp-3、mefp-4、mefp-5、mefp-6、胶原蛋白pre-COL-P、pre-COL-D、pre-COL-NG、足丝基质蛋白PTMP和DTMP中的一种或几种的混合物。在本文中使用的贻贝粘蛋白在水溶液中的酸碱度可以是pH 1.0-7.0,特别是可以在pH 3.0-6.5的范围内以使其治疗效果更佳。Mussel mucin used herein refers to Mytilus edulis Linnaeus, Mytilus coruscus or Perna viridis from the Mytilidae bivalve mollusc. 11 subclasses of mussel mucin, currently known as purified from marine mussels: mefp1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, collagen pre-COL- A mixture of one or more of P, pre-COL-D, pre-COL-NG, foot silk matrix proteins PTMP and DTMP. The mussel mucin used herein may have a pH of 1.0 to 7.0 in an aqueous solution, and particularly may be in the range of pH 3.0 to 6.5 to make the therapeutic effect better.

在本文中使用的贻贝粘蛋白可以采用以下制备方法获得,例如中国专 利号ZL200710179491.0的一种使用混合吸附色谱分离纯化贻贝粘蛋白的方法,中国专利号ZL200710179492.5的一种使用羧甲基离子交换色谱纯化贻贝粘蛋白的方法,中国专利号ZL200910087567.6的一种使用盐析和透析分离纯化贻贝粘蛋白的方法等。The mussel mucin used herein can be obtained by the following preparation methods, such as Chinese A method for separating and purifying mussel mucin using mixed adsorption chromatography, ZL200710179491.0, Chinese Patent No. ZL200710179492.5, a method for purifying mussel mucin using carboxymethyl ion exchange chromatography, Chinese Patent No. ZL200910087567. A method for separating and purifying mussel mucin using salting out and dialysis, and the like.

在本文中使用的贻贝粘蛋白可以是溶液或冻干粉形式,特别是贻贝粘蛋白在产品中的浓度可以是0.1-15.0mg/ml,当浓度过低时,贻贝粘蛋白的功效不大,当浓度过高时,可引起细胞毒性、皮肤刺激等作用,从而不利于软组织炎症的治疗。The mussel mucin used herein may be in the form of a solution or a lyophilized powder, in particular, the concentration of mussel mucin in the product may be 0.1-15.0 mg/ml, and when the concentration is too low, the effect of mussel mucin Not large, when the concentration is too high, it can cause cytotoxicity, skin irritation, etc., which is not conducive to the treatment of soft tissue inflammation.

在本文中使用的贻贝粘蛋白也可以与辅料结合而制备成液体剂。示例性的贻贝粘蛋白液体剂是将贻贝粘蛋白溶液母液或冻干粉溶解或稀释至一定浓度或pH值制得,溶解或稀释用溶液可以是水、生理盐水、磷酸盐溶液、醋酸盐溶液、硼酸盐溶液等等。最终产品中贻贝粘蛋白的酸碱度可以是pH1.0-7.0,特别是可以在pH 3.0-6.5的范围内治疗效果更佳。The mussel mucin used herein can also be prepared as a liquid agent by combining it with an excipient. An exemplary mussel mucin liquid preparation is prepared by dissolving or diluting mussel mucin solution mother liquor or lyophilized powder to a certain concentration or pH, and the solution for dissolving or diluting may be water, physiological saline, phosphate solution, vinegar. Acid solution, borate solution, and the like. The pH of mussel mucin in the final product may be pH 1.0-7.0, and in particular, the therapeutic effect may be better in the range of pH 3.0-6.5.

在本文中使用的贻贝粘蛋白也可以与辅料结合而制备成凝胶剂。示例性的贻贝粘蛋白凝胶剂是将贻贝粘蛋白溶液或冻干粉与凝胶基质材料混合制得,所述凝胶基质材料可以是选自纤维素衍生物、卡波姆和海藻酸盐、西黄蓍胶、明胶、果胶、卡拉胶、结冷胶、淀粉、黄原胶、阳离子瓜尔胶、琼脂、非纤维素多糖、乙烯聚合物、丙烯酸树脂、聚乙烯醇或聚羧乙烯中之一或其任意组合。The mussel mucin used herein can also be prepared as a gelling agent in combination with an excipient. An exemplary mussel mucin gel is prepared by mixing a mussel mucin solution or a lyophilized powder with a gel matrix material, which may be selected from the group consisting of cellulose derivatives, carbomers, and seaweeds. Acid salt, tragacanth, gelatin, pectin, carrageenan, gellan gum, starch, xanthan gum, cationic guar gum, agar, non-cellulosic polysaccharide, ethylene polymer, acrylic resin, polyvinyl alcohol or poly One of carboxyvinyl or any combination thereof.

本领域技术人员可以根据不同病期的临床适应症的特点来选择使用上述剂型或其他合适的剂型。One skilled in the art can select to use the above dosage forms or other suitable dosage forms depending on the characteristics of the clinical indications at different stages of the disease.

以上所有制剂都可以采用本领域周知的方法制备,详细的操作步骤可以参照例如《制剂学》。All of the above preparations can be prepared by methods well known in the art, and detailed procedures can be referred to, for example, "Pharmaceutics".

在本文中使用的贻贝粘蛋白可以作为主要原料,采用药学上可接受的载体制备药品。所述药品可以是液体剂、凝胶剂。所述药品可通过口服、喷涂、注射、定向局部缓释、靶向给药的方式使用,并且可以以低温或者加热的方式给予。The mussel mucin used herein can be used as a main raw material to prepare a medicine using a pharmaceutically acceptable carrier. The drug may be a liquid agent or a gel. The drug may be administered by oral, spray, injection, targeted topical sustained release, targeted administration, and may be administered at a low temperature or in a heated manner.

在本文中使用的贻贝粘蛋白可以作为主要原料,制备医疗器械。本文中使用的术语医疗器械是指直接或间接用于人体的材料及其他类似或相关的物品。所述医疗器械可以是液体剂、凝胶剂、泡沫剂。所述医疗器械可 通过口服、喷涂、注射、定向局部缓释、靶向给药的方式使用,并且可以以低温或加热方式给予。The mussel mucin used herein can be used as a main raw material to prepare a medical device. The term medical device as used herein refers to materials that are used directly or indirectly to the human body and other similar or related items. The medical device may be a liquid agent, a gel, or a foaming agent. The medical device can It is used by oral administration, spraying, injection, targeted local sustained release, targeted administration, and can be administered at a low temperature or in a heated manner.

在本文中使用的贻贝粘蛋白可以作为主要原料,采用保健品或食品领域可接受的辅料制备保健品或食品。所述保健品或食品可以是液体剂、凝胶剂。所述保健品或食品可通过口服、喷涂、注射、定向局部缓释、靶向给药的方式使用,并且可以以低温或加热方式给予。The mussel mucin used herein can be used as a main raw material, and a health care product or food can be prepared by using an excipient which is acceptable in the field of health care or food. The health care product or food may be a liquid agent or a gel. The health supplement or food may be administered by oral, spray, injection, targeted topical sustained release, targeted administration, and may be administered at a low temperature or in a heated manner.

本发明的另一个目的是提供贻贝粘蛋白产品抑制软组织炎症的应用。Another object of the invention is to provide the use of mussel mucin products to inhibit soft tissue inflammation.

出人意料地,本发明人发现贻贝粘蛋白可缓解各种软组织炎症,如肌肉、韧带、筋膜、肌腱、滑膜、脂肪、关节囊、淋巴组织的挫伤或裂伤。Surprisingly, the inventors have found that mussel mucin can alleviate various soft tissue inflammations such as muscles, ligaments, fascia, tendons, synovial membranes, fat, joint capsules, and contusions or lacerations of lymphoid tissues.

肌肉炎是指因慢性损伤、风寒湿邪、感染、肌肉痉挛等因素引起肌肉或肌腱及附着处或腱鞘的慢性炎症。Musitis refers to chronic inflammation of muscles or tendons and attachments or tendon sheaths due to chronic damage, wind and cold dampness, infection, muscle spasms and other factors.

韧带炎是一种慢性的不红、不肿、不发热、有痛的无菌性炎症损伤。韧带炎治疗以理疗为主,同时辅以芬必得等非甾体抗炎药物。Ligamentitis is a chronic, non-red, non-swelling, non-fever, painful aseptic inflammatory injury. The treatment of ligamentitis is based on physiotherapy, supplemented by non-steroidal anti-inflammatory drugs such as fenbide.

筋膜炎是发生于肌筋膜的一种非特异性炎症。可发生于全身各个部位,多见于腰部、髂骨后嵴及肩胛区域。非甾体类抗炎药物如布洛芬和双氯芬酸为治疗筋膜炎的常用药物。Fasciitis is a non-specific inflammation that occurs in the myofascial fascia. Can occur in all parts of the body, more common in the waist, the posterior tibial and the scapular region. Non-steroidal anti-inflammatory drugs such as ibuprofen and diclofenac are commonly used drugs for the treatment of fasciitis.

肌腱炎是指由于肌肉纤维过度使用,反复强烈牵拉而引起肌腱胶原纤维退行性病变,除了累及肌腱本身,还可以累及腱鞘。大多数情况下,常合并受累肌腱胶原组织变性,因此现在通称为肌腱病。肌腱炎使用非甾体抗炎药物缓解疼痛,严重的疼痛,可以局部注射类固醇激素。然而多次注射类固醇会减弱肌腱的强度,导致肌腱断裂。Tendinitis refers to the degenerative pathological changes of tendon collagen fibers caused by excessive use of muscle fibers and repeated intense pulling. In addition to involving the tendon itself, it can also involve the tendon sheath. In most cases, it is often associated with the degeneration of collagen tissue in the affected tendon, so it is now known as tendinopathy. Tendinitis uses non-steroidal anti-inflammatory drugs to relieve pain, severe pain, and local injection of steroids. However, multiple injections of steroids weaken the strength of the tendon and cause the tendon to break.

滑膜炎是一种无菌型炎症,是由于关节扭伤和多种关节内损伤而引起的。滑膜的功能异常会导致关节液无法正常生成和吸收,关节就会产生积液。滑膜的形态改变还会侵袭关节软骨,不及时治疗会导致关节骨性关节炎,存在致残危机。Synovitis is a form of aseptic inflammation caused by joint sprains and multiple intra-articular injuries. Abnormal function of the synovial membrane can cause the joint fluid to fail to form and absorb normally, and the joint will produce fluid accumulation. The morphological changes of the synovial membrane can also invade the articular cartilage. If it is not treated in time, it will lead to osteoarthritis of the joints, and there is a disability crisis.

脂肪炎是皮下脂肪细胞所构成的小叶及小叶间的结缔组织损伤引起的炎症。临床表现缺乏特异性,以淡红色至棕褐色的皮下结节或斑块较为多见,大小、数目不定,自觉疼痛和压痛。Lipitis is inflammation caused by damage to connective tissue between the lobule and the lobule composed of subcutaneous fat cells. The clinical manifestations lack specificity. The subcutaneous nodules or plaques are light red to tan, and the size and number are uncertain, and the pain and tenderness are conscious.

关节囊炎是关节囊的急性或慢性炎症,是由直接暴力损伤、关节屈、伸、外展、外旋等动作过度,经反复、长期、持续的磨擦和压迫导致的炎 症。临床表现为疼痛、局限性压痛、活动受限、肿胀等。关节囊炎治疗采用休息或患部制动和大剂量非甾体抗炎药物,必要时使用麻醉镇静剂。Joint capsule inflammation is an acute or chronic inflammation of the joint capsule. It is caused by direct violent injury, joint flexion, extension, abduction, external rotation, etc., caused by repeated, long-term, continuous friction and compression. disease. Clinical manifestations include pain, localized tenderness, limited mobility, and swelling. The treatment of joint capsule is treated with rest or affected part of the brakes and high-dose non-steroidal anti-inflammatory drugs, if necessary, anesthesia sedatives.

淋巴组织炎是由淋巴结所属引流区域的急、慢性炎症累及淋巴结所引起的非特异性炎症,如上肢、乳腺、胸壁、背部和脐以上腹壁的感染引起腋部淋巴结炎;下肢、脐以下腹壁、会阴和臀部的感染可以发生腹股沟部淋巴结炎;头、面、口腔、颈部和肩部感染,引起颌下及颈部的淋巴结炎。出人意料地,本发明人发现并证实了贻贝粘蛋白可用于治疗肌肉、韧带、筋膜、肌腱、滑膜、脂肪、关节囊、淋巴组织的挫伤或裂伤引起的软组织炎症等。本发明的贻贝粘蛋白可外用,通过透皮吸收直接作用于患处,也可以被吸收后发挥抗炎药理作用。此外,贻贝粘蛋白作为广谱抗炎制剂不会引起其它组织或器官的损伤。Lymphadenitis is a non-specific inflammation caused by acute and chronic inflammation involving lymph nodes in the drainage area of the lymph nodes. The infection of the upper limbs, breast, chest wall, back and ventral wall of the umbilicus causes axillary lymphadenitis; lower limbs, abdominal wall below the umbilicus, perineum Infections in the buttocks can occur in the inguinal lymphadenitis; infections in the head, face, mouth, neck and shoulders cause lymphadenitis in the submandibular and neck. Surprisingly, the inventors have discovered and confirmed that mussel mucin can be used to treat soft tissue inflammation caused by contusions or lacerations of muscles, ligaments, fascia, tendons, synovial membranes, fat, joint capsules, lymphoid tissues, and the like. The mussel mucin of the present invention can be used externally, directly acts on the affected part by transdermal absorption, and can also be absorbed to exert an anti-inflammatory pharmacological action. In addition, mussel mucin as a broad-spectrum anti-inflammatory agent does not cause damage to other tissues or organs.

附图说明DRAWINGS

图1示出本发明的贻贝粘蛋白液体药品用于肌肉组织炎症治疗,上图为治疗第0天,下图为第21天的结果。Fig. 1 shows a mussel mucin liquid medicine of the present invention for use in treatment of muscle tissue inflammation, the upper graph being the day of treatment on day 0, and the lower panel being the result on day 21.

具体实施方式detailed description

本发明的实施方式包括:Embodiments of the invention include:

1、贻贝粘蛋白在治疗软组织炎症中的应用。1. The application of mussel mucin in the treatment of soft tissue inflammation.

2、根据实施方式1的贻贝粘蛋白应用,其中所述贻贝粘蛋白是来自亚类:mefp1、mefp-2、mefp-3、mefp-4、mefp-5、mefp-6、胶原蛋白pre-COL-P、pre-COL-D、pre-COL-NG、足丝基质蛋白PTMP和DTMP中的一种或几种的混合物。2. The mussel mucin application according to embodiment 1, wherein the mussel mucin is from a subclass: mefp1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, collagen pre a mixture of one or more of -COL-P, pre-COL-D, pre-COL-NG, foot silk matrix protein PTMP and DTMP.

3、根据实施方式1的贻贝粘蛋白应用,其中所述贻贝粘蛋白浓度可以是0.1-15.0mg/ml。3. The mussel mucin application according to embodiment 1, wherein the mussel mucin concentration may be from 0.1 to 15.0 mg/ml.

4、根据实施方式1的贻贝粘蛋白应用,其中所述贻贝粘蛋白可以是以液体剂、凝胶剂使用。4. The mussel mucin application according to embodiment 1, wherein the mussel mucin is used as a liquid agent or a gel.

5、根据实施方式1的贻贝粘蛋白应用,其中最终产品中的贻贝粘蛋白可以是在pH 1.0-7.0的范围内,特别是在pH 3.0-6.5的范围内。5. Mussel mucin application according to embodiment 1, wherein the mussel mucin in the final product may be in the range of pH 1.0-7.0, in particular in the range of pH 3.0-6.5.

6、根据实施方式1-5中任一项的贻贝粘蛋白应用,其中所述软组织炎 症可以选自:肌肉、韧带、筋膜、肌腱、滑膜、脂肪、关节囊、淋巴组织的挫伤或裂伤引起的软组织炎症。The mussel mucin application according to any one of embodiments 1 to 5, wherein the soft tissue inflammation The disease can be selected from the group consisting of: muscle, ligament, fascia, tendon, synovium, fat, joint capsule, lymphoid tissue contusion or laceration caused by soft tissue inflammation.

7、贻贝粘蛋白作为活性成分在用于治疗软组织炎症的组合物中的应用,其中所述组合物可以是以液体剂、凝胶剂使用。7. Use of mussel mucin as an active ingredient in a composition for treating inflammation of a soft tissue, wherein the composition may be used as a liquid or gel.

8、根据实施方式7的贻贝粘蛋白应用,其中所述组合物可以是通过口服、喷涂、注射、定向局部缓释、靶向给药的方式使用。8. The mussel mucin application according to embodiment 7, wherein the composition can be used by oral, spray, injection, targeted local sustained release, targeted administration.

9、根据实施方式7的贻贝粘蛋白应用,其中所述组合物可以以低温或加热方式使用。9. Mussel mucin application according to embodiment 7, wherein the composition can be used at low temperature or in a heated manner.

10、一种用于治疗软组织炎症的药品,包括贻贝粘蛋白和药学上可接受的载体,其中贻贝粘蛋白的浓度可以是0.1-15.0mg/ml。10. A medicament for the treatment of soft tissue inflammation comprising mussel mucin and a pharmaceutically acceptable carrier, wherein the mussel mucin is present in a concentration of from 0.1 to 15.0 mg/ml.

11、一种用于治疗软组织炎症的医疗器械,包括贻贝粘蛋白和医疗器械领域可接受的载体,其中贻贝粘蛋白的浓度可以是0.1-15.0mg/ml。11. A medical device for treating inflammation of a soft tissue comprising a mussel mucin and a carrier acceptable for use in the field of medical devices, wherein the concentration of mussel mucin may be from 0.1 to 15.0 mg/ml.

12、一种用于治疗软组织炎症的保健品/食品,包括贻贝粘蛋白和保健品或食品领域可接受的载体,其中贻贝粘蛋白的浓度可以是0.1-15.0mg/ml。12. A health supplement/food for treating soft tissue inflammation, comprising mussel mucin and a health care product or a carrier acceptable for the food field, wherein the mussel mucin concentration may be from 0.1 to 15.0 mg/ml.

13、贻贝粘蛋白在用于治疗软组织炎症的药品中的应用,其中所述软组织炎症可以选自:肌肉、韧带、筋膜、肌腱、滑膜、脂肪、关节囊、淋巴组织的挫伤或裂伤引起的软组织炎症。13. Use of mussel mucin in a medicament for treating inflammation of a soft tissue, wherein the soft tissue inflammation may be selected from the group consisting of muscles, ligaments, fascia, tendons, synovium, fat, joint capsule, and contusion or crack of lymphoid tissue. Soft tissue inflammation caused by injury.

14、贻贝粘蛋白在用于治疗软组织炎症的医疗器械中的应用,其中所述软组织炎症可以选自:肌肉、韧带、筋膜、肌腱、滑膜、脂肪、关节囊、淋巴组织的挫伤或裂伤引起的软组织炎症。14. The use of mussel mucin in a medical device for treating soft tissue inflammation, wherein the soft tissue inflammation can be selected from the group consisting of muscles, ligaments, fascia, tendons, synovium, fat, joint capsule, lymphoid tissue contusion or Soft tissue inflammation caused by laceration.

15、贻贝粘蛋白在用于治疗软组织炎症的保健品或食品中的应用,其中所述软组织炎症可以选自:肌肉、韧带、筋膜、肌腱、滑膜、脂肪、关节囊、淋巴组织的挫伤或裂伤引起的软组织炎症。15. The use of mussel mucin in a health care product or food for treating soft tissue inflammation, wherein the soft tissue inflammation can be selected from the group consisting of: muscle, ligament, fascia, tendon, synovium, fat, joint capsule, lymphoid tissue. Soft tissue inflammation caused by contusion or laceration.

16、一种治疗软组织炎症的方法,包括配制根据前述实施方式10-12中任一种的贻贝粘蛋白液体剂或凝胶剂,并给予有需要的受试者,其中贻贝粘蛋白的浓度可以是0.1-15.0mg/ml。16. A method of treating inflammation of a soft tissue comprising formulating a mussel mucoid liquid or gel according to any one of the preceding embodiments 10-12 and administering to a subject in need thereof, wherein mussel mucin The concentration can be from 0.1 to 15.0 mg/ml.

17、根据实施方式16的方法,其中所述软组织炎症可以选自:肌肉、韧带、筋膜、肌腱、滑膜、脂肪、关节囊、淋巴组织的挫伤或裂伤引起的软组织炎症。 17. The method of embodiment 16, wherein the soft tissue inflammation is selected from the group consisting of: muscle, ligament, fascia, tendon, synovial membrane, fat, joint capsule, contusion of a lymphoid tissue or soft tissue inflammation caused by a laceration.

下面将结合具体实施例对本发明作进一步说明。需要指出的是,由本发明中的贻贝粘蛋白或贻贝粘蛋白的各种制剂形成的药品、医疗器械、保健品或食品在施用于受试者后,都可以应用于上文所述的适应症并展现出上文所述的功能,在本发明范围内的所有剂型均已测试,下文中,仅仅是为说明,只在实施例中描述了其中一少部分,然而不应将其理解为对本发明的限制。The invention will now be further described in conjunction with specific embodiments. It should be noted that the pharmaceutical, medical device, health care product or food formed by various preparations of mussel mucin or mussel mucin in the present invention can be applied to the above as described above after administration to a subject. Indications and exhibiting the functions described above, all dosage forms within the scope of the invention have been tested, hereinafter, for illustrative purposes only a few of which are described in the examples, but should not be understood To limit the invention.

除非特殊说明,否则本发明中所使用的试剂都是市售可购买的。Unless otherwise stated, the reagents used in the present invention are commercially available.

实施例1:贻贝粘蛋白凝胶剂药品在腿部肌肉损伤治疗中的应用。Example 1: Application of mussel mucin gel drug in the treatment of leg muscle injury.

取贻贝粘蛋白溶液,与瓜尔胶、丙三醇按体积比2:1:1混合,加入注射水,用柠檬酸调整至pH 3.0,制备贻贝粘蛋白含量为1.5mg/ml的贻贝粘蛋白凝胶剂药品。The mussel mucin solution was taken, mixed with guar gum and glycerol at a volume ratio of 2:1:1, and water was added thereto, and the pH was adjusted to 3.0 with citric acid to prepare a mussel mucoprotein content of 1.5 mg/ml. Shell mucin gel drug.

收集经骨科专家确诊的腿部肌肉损伤患者10例,入选病例临床表现为伤处疼痛、肿胀、压痛或痉挛。入选病例随机分配至对照组或试验组,对照组采用云南白药气雾剂治疗,每日2次,用量需能均匀覆盖患处;试验组采用贻贝粘蛋白凝胶剂药品涂抹患处,每日2次,用量需能均匀覆盖患处。用药后对照组无明显变化,试验组10-30分钟内患处疼痛明显减弱,从治疗前视觉模拟VAS评分4.0-6.0下降到1.0-3.0,止痛时间可持续2-5小时。并且,随着使用间隔延长,未表现出任何依赖性。Ten patients with leg muscle injury diagnosed by orthopedic specialists were collected. The clinical manifestations of the selected cases were pain, swelling, tenderness or spasm. The selected cases were randomly assigned to the control group or the experimental group. The control group was treated with Yunnan Baiyao aerosol for 2 times a day. The dosage should be able to cover the affected area evenly. The test group used mussel mucin gel drug to spread the affected area. Second, the dosage should be able to cover the affected area evenly. There was no significant change in the control group after administration. The pain in the affected area was significantly weakened in the test group within 10-30 minutes. The visual analog VAS score decreased from 4.0-6.0 to 1.0-3.0 before treatment, and the analgesic time lasted for 2-5 hours. Also, as the use interval is extended, no dependence is exhibited.

连续使用7天后,试验组全部病患损伤部位疼痛及肿胀症状消失(表1),对照组至使用14天左右全部病患损伤部位疼痛及肿胀症状消失。可以看出,贻贝粘蛋白凝胶剂药品可用于肌肉损伤的治疗,且效果较传统药物更佳。After 7 days of continuous use, the pain and swelling symptoms of the injured part of the test group disappeared (Table 1), and the pain and swelling symptoms of the injured part of the control group disappeared after about 14 days. It can be seen that mussel mucin gel drugs can be used for the treatment of muscle damage, and the effect is better than traditional drugs.

表1:Table 1:

观察指标Observation index 对照组Control group 试验组test group 平均起效时间(min)Average onset time (min) 无缓解No relief 19.5±7.919.5±7.9 使用前VAS平均评分VAS average score before use 4,3±0.94,3±0.9 4.4±0.44.4±0.4 使用后VAS平均评分VAS average score after use 4,3±0.94,3±0.9 1.9±0.71.9±0.7 平均止痛持续时间(h)Average pain relief duration (h) 无缓解No relief 3.2±1.03.2±1.0 平均康复时间(天)Average recovery time (days) 12.9±3.212.9±3.2 5.7±0.85.7±0.8

实施例2:贻贝粘蛋白液体医疗器械在踝部韧带损伤治疗中的应用。Example 2: Application of mussel mucin liquid medical device in the treatment of ankle ligament injury.

取浓度为0.5mg/ml的贻贝粘蛋白溶液,用0.001%的乙酸稀释5倍,至贻贝粘蛋白含量为0.1mg/ml,得到贻贝粘蛋白液体医疗器械。A mussel mucin solution having a concentration of 0.5 mg/ml was prepared, diluted 5 times with 0.001% acetic acid, and the mussel mucin content was 0.1 mg/ml to obtain a mussel mucin liquid medical device.

收集经骨科专家确诊的踝部韧带撕裂伤患者10例,入选病例临床表现为伤处疼痛、肿胀、压痛及皮下出血(可见青紫区)。入选病例随机分配至对照组或试验组,对照组采用云南白药气雾剂,每日3次,用量需能均匀覆盖患处;试验组入选病例采用贻贝粘蛋白液体药品喷涂患处,每日3次,用量需能均匀覆盖患处。使用后对照组患处疼痛无缓解,试验组20-40分钟内患处疼痛明显减弱,从治疗前视觉模拟VAS评分4.0-6.0下降到1.0-3.0,止痛时间可持续2-5小时。并且,随着使用间隔延长,未表现出任何依赖性。Ten patients with ankle ligament laceration diagnosed by orthopedic specialists were collected. The clinical manifestations of the selected cases were pain, swelling, tenderness and subcutaneous hemorrhage (see the cyanosis area). The selected cases were randomly assigned to the control group or the experimental group. The control group was treated with Yunnan Baiyao aerosol for 3 times a day. The dosage should be able to cover the affected area evenly. The selected cases were sprayed with mussel mucin liquid medicine for 3 times a day. The dosage should be able to cover the affected area evenly. After the use, the pain in the control group was not relieved. The pain in the affected area was significantly weakened in the test group within 20-40 minutes. The visual analog VAS score was 4.0-6.0 before treatment to 1.0-3.0, and the analgesic time lasted 2-5 hours. Also, as the use interval is extended, no dependence is exhibited.

连续喷涂6天后,试验组全部受试者损伤部位疼痛及肿胀症状消失;连续使用12天后对照组全部受试者损伤部位疼痛及肿胀症状消失(表2)。可以看出,贻贝粘蛋白液体医疗器械可用于韧带损伤的治疗,且效果较传统药品更佳。After 6 days of continuous spraying, the pain and swelling symptoms of the injured part disappeared in all subjects in the test group; after 12 days of continuous use, the pain and swelling symptoms of the injured part disappeared in all subjects in the control group (Table 2). It can be seen that the mussel mucin liquid medical device can be used for the treatment of ligament injury, and the effect is better than the traditional medicine.

表2:Table 2:

观察指标Observation index 对照组Control group 试验组test group 平均起效时间(min)Average onset time (min) 无缓解No relief 33.8±5.433.8±5.4 使用前VAS平均评分VAS average score before use 4.9±0.24.9±0.2 4.8±0.54.8±0.5 使用后VAS平均评分VAS average score after use 4.9±0.24.9±0.2 1.6±0.81.6±0.8 平均止痛持续时间(h)Average pain relief duration (h) 无缓解No relief 4.0±0.74.0±0.7 平均康复时间(天)Average recovery time (days) 10.6±0.810.6±0.8 4.9±1.04.9±1.0

实施例3:贻贝粘蛋白液体药品在筋膜炎治疗中的应用。Example 3: Application of mussel mucin liquid medicine in the treatment of fasciitis.

取浓度为10.0mg/ml的贻贝粘蛋白溶液,用0.01%的柠檬酸稀释,至贻贝粘蛋白含量为1.0mg/ml,得到贻贝粘蛋白液体药品。A mussel mucin solution having a concentration of 10.0 mg/ml was diluted with 0.01% citric acid to a mussel mucin content of 1.0 mg/ml to obtain a mussel mucin liquid medicine.

收集经骨科专家确诊的腰部纤维炎患者2例,入选病例临床表现为患处持续性疼痛,超声检查可见筋膜有明显裂隙。2例患者随机分入对照组和试验组,采用微创手术治疗,切除结节,修补筋膜,分离粘连及切除皮神 经后,对照组不做处理,试验组局部注射贻贝粘蛋白液体药品0.5ml。治疗1周后复查,对照组有轻微疼痛症状,但筋膜裂隙仍可见;对照组无疼痛症状,筋膜裂隙已愈合。可以看出,贻贝粘蛋白液体药品可用于筋膜炎的治疗。Two patients with lumbar fibrosis diagnosed by orthopedic specialists were collected. The clinical manifestations of the selected cases were persistent pain in the affected area. Ultrasound examination revealed obvious fissures in the fascia. Two patients were randomly assigned to the control group and the experimental group. Minimally invasive surgery was performed to remove the nodules, repair the fascia, separate the adhesions and remove the skin. After the passage, the control group was not treated, and the test group was locally injected with 0.5 ml of mussel mucin liquid medicine. After 1 week of treatment, the control group had mild pain symptoms, but the fascial fissures were still visible; the control group had no pain symptoms, and the fascial fissures had healed. It can be seen that mussel mucin liquid medicine can be used for the treatment of fasciitis.

实施例4:贻贝粘蛋白凝胶剂医疗器械在肌腱损伤治疗中的应用。Example 4: Application of mussel mucin gel medical device in the treatment of tendon injury.

取羟丙基甲基纤维素10g,加入20ml去离子水,90℃温浴30min至完全溶解得到凝胶基质,另取浓度为10.0mg/ml的贻贝粘蛋白溶液2.5ml,边搅拌边加入到凝胶基质中,混合均匀后形成贻贝粘蛋白凝胶医疗器械,其中贻贝粘蛋白浓度为1.0mg/ml。Take 10g of hydroxypropyl methylcellulose, add 20ml of deionized water, warm bath at 90 °C for 30min to completely dissolve to obtain the gel matrix, and take another 2.5ml mussel mucin solution with a concentration of 10.0mg/ml, and add to the mixture while stirring. In the gel matrix, after mixing uniformly, a mussel mucin gel medical device was formed, wherein the mussel mucin concentration was 1.0 mg/ml.

收集经骨科专家确诊的跟腱损伤患者6例,入选病例临床表现为伤处疼痛、肿胀、压痛。入选病例采用贻贝粘蛋白凝胶剂医疗器械喷涂患处,每日2次,用量需能均匀覆盖患处。使用后10-25分钟内患处疼痛明显减弱,从治疗前视觉模拟VAS评分4.0-5.0下降到1.0-3.0,止痛时间可持续2-5小时。并且,随着使用间隔延长,未表现出任何依赖性。Six patients with Achilles tendon injury diagnosed by orthopedic specialists were collected. The clinical manifestations of the selected cases were pain, swelling and tenderness. In the selected cases, the affected area was sprayed with mussel mucin gel medical device twice a day, and the dosage should be evenly covered. Pain in the affected area was significantly attenuated within 10-25 minutes after use, from a visual analog VAS score of 4.0-5.0 before treatment to 1.0-3.0, and an analgesic time of 2-5 hours. Also, as the use interval is extended, no dependence is exhibited.

连续喷涂1周后,全部受试者损伤部位疼痛及肿胀症状消失(表3)。可以看出,贻贝粘蛋白凝胶医疗器械可用于跟腱损伤的治疗。After 1 week of continuous spraying, pain and swelling symptoms at the injury site disappeared in all subjects (Table 3). It can be seen that mussel mucin gel medical devices can be used for the treatment of Achilles tendon injuries.

表3:table 3:

观察指标Observation index 平均数值Average value 平均起效时间(min)Average onset time (min) 11.6±3.911.6±3.9 使用前VAS平均评分VAS average score before use 4.2±0.54.2±0.5 使用后VAS平均评分VAS average score after use 1.3±0.81.3±0.8 平均止痛持续时间(h)Average pain relief duration (h) 3.4±0.83.4±0.8 平均康复时间(天)Average recovery time (days) 5.3±1.25.3±1.2

实施例5:贻贝粘蛋白凝胶剂医疗器械在膝关节滑膜炎治疗中的应用。Example 5: Application of mussel mucin gel medical device in the treatment of knee joint synovitis.

取贻贝粘蛋白溶液,与瓜尔胶、丙三醇按质量比为2:1:1混合,用生理盐水稀释,用醋酸调整酸碱度到pH 5.0得到贻贝粘蛋白水凝胶医疗器械,其中贻贝粘蛋白浓度为2.0mg/ml。Taking the mussel mucin solution, mixing with guar gum and glycerol at a mass ratio of 2:1:1, diluting with physiological saline, adjusting the pH to pH 5.0 with acetic acid to obtain a mussel mucin hydrogel medical device, wherein The mussel mucin concentration was 2.0 mg/ml.

收集经骨科专家确诊的膝关节滑膜炎患者5例,入选病例临床表现为 伤处疼痛、肿胀、活动困难。入选病例采用贻贝粘蛋白水凝胶医疗器械喷涂患处,每日2次,用量需能均匀覆盖患处。连续喷涂1周后,全部受试者损伤部位疼痛及肿胀症状消失。可以看出,贻贝粘蛋白水凝胶医疗器械可用于滑膜炎的治疗。Five patients with knee synovitis diagnosed by orthopedic specialists were collected. The clinical manifestations of the selected cases were Pain, swelling, and difficulty in movement. The selected cases were sprayed with mussel mucin hydrogel medical equipment twice a day, and the dosage should be able to cover the affected area evenly. After 1 week of continuous spraying, the pain and swelling symptoms of the injured part of all subjects disappeared. It can be seen that mussel mucin hydrogel medical devices can be used for the treatment of synovitis.

实施例6:贻贝粘蛋白液体药品在扁桃体炎治疗中的应用。Example 6: Application of mussel mucin liquid medicine in the treatment of tonsillitis.

取浓度为10.0mg/ml的贻贝粘蛋白溶液,用0.01%的柠檬酸稀释,至贻贝粘蛋白含量为0.5mg/ml,得到贻贝粘蛋白液体药品。A mussel mucin solution having a concentration of 10.0 mg/ml was diluted with 0.01% citric acid to a mussel mucin content of 0.5 mg/ml to obtain a mussel mucin liquid medicine.

收集经耳鼻喉科专家确诊的急性扁桃体炎患者10例,入选病例临床表现为患者全身发热、咽痛明显。入选病例随机分配到对照组或试验组,对照组采用口服青霉素治疗,每日2次;试验组病例采用贻贝粘蛋白液体药品漱口,并喷涂于咽喉处,每日3次,饭后使用。治疗2天后,对照组病患发热症状消失,咽痛缓解;试验组病患发热症状消失,咽痛缓解。治疗4天后,对照组和试验组全部病患体温正常,咽痛症状消失。可以看出,贻贝粘蛋白液体药品可用于扁桃体炎的治疗。Ten patients with acute tonsillitis diagnosed by otolaryngologists were collected. The clinical manifestations of the patients were systemic fever and sore throat. The selected cases were randomly assigned to the control group or the experimental group. The control group was treated with oral penicillin twice a day. The test group was treated with mussel mucin liquid medicine and sprayed on the throat 3 times a day. . After 2 days of treatment, the fever symptoms of the control group disappeared and the sore throat was relieved; the fever symptoms disappeared and the sore throat was relieved in the test group. After 4 days of treatment, all the patients in the control group and the test group had normal body temperature and the symptoms of sore throat disappeared. It can be seen that mussel mucin liquid medicine can be used for the treatment of tonsillitis.

实施例7:贻贝粘蛋白液体药品在慢性难愈合炎症性创面治疗中的应用Example 7: Application of mussel mucin liquid medicine in the treatment of chronic refractory inflammatory wounds

采用柱层析法制备贻贝粘蛋白溶液(MAP),蛋白浓度为5.0mg/ml,纯度90%。取上述的贻贝粘蛋白溶液,用生理盐水稀释,至贻贝粘蛋白含量为0.5mg/ml,得到贻贝粘蛋白液体药品。每100ml贻贝粘蛋白产品中含有贻贝粘蛋白0.5mg,氯化钠0.9g,其余为注射用水。The mussel mucin solution (MAP) was prepared by column chromatography with a protein concentration of 5.0 mg/ml and a purity of 90%. The above mussel mucin solution was taken and diluted with physiological saline to a mussel mucin content of 0.5 mg/ml to obtain a mussel mucin liquid medicine. Each 100 ml mussel mucin product contains mussel mucin 0.5 mg, sodium chloride 0.9 g, and the rest is water for injection.

收集慢性难愈合炎症性创面患者12例,经外科专家确诊为慢性创面,入选病例临床表现为患者腿部或足部有长期未愈合创面,溃烂部位深度可达到真皮下层、肌肉层或骨面。Twelve patients with chronic refractory inflammatory wounds were collected and diagnosed as chronic wounds by surgical experts. The clinical manifestations of the patients were long-term unhealed wounds in the legs or feet of the patients. The depth of the ulcerated sites could reach the subdermal, muscular or bone surface.

入选病例随机分配到对照组或试验组,对照组采用原去腐生肌膏(阻创牌,魏氏泰生堂制药)治疗,每日2次;试验组病例采用贻贝粘蛋白液体药品治疗,每日2次。治疗21天后,对照组6例病患慢性创面均未见明显好转。试验组6例病患中有3例基本愈合,另外3例愈合率达到90%以上。贻贝粘蛋白液体药品可用于慢性难愈合炎症性创面的治疗,可用于修复受损的肌肉组织。 The selected cases were randomly assigned to the control group or the experimental group. The control group was treated with the original succulent muscle cream (Jie Chuang, Wei Shi Tai Tang Tang Pharmaceutical) twice a day. The test group was treated with mussel mucin liquid medicine. 2 times a day. After 21 days of treatment, the chronic wounds of 6 patients in the control group showed no significant improvement. In the experimental group, 3 of the 6 patients basically healed, and the other 3 patients achieved a healing rate of more than 90%. Mussel mucin liquid medicine can be used for the treatment of chronic refractory inflammatory wounds and can be used to repair damaged muscle tissue.

Claims (10)

贻贝粘蛋白在治疗软组织炎症中的应用。The application of mussel mucin in the treatment of soft tissue inflammation. 根据权利要求1的贻贝粘蛋白应用,其中所述贻贝粘蛋白是来自亚类:mefp1、mefp-2、mefp-3、mefp-4、mefp-5、mefp-6、胶原蛋白pre-COL-P、pre-COL-D、pre-COL-NG、足丝基质蛋白PTMP和DTMP中的一种或几种的混合物。The mussel mucin application according to claim 1, wherein said mussel mucin is from a subclass: mefp1, mefp-2, mefp-3, mefp-4, mefp-5, mefp-6, collagen pre-COL a mixture of one or more of -P, pre-COL-D, pre-COL-NG, foot silk matrix proteins PTMP and DTMP. 根据权利要求1的贻贝粘蛋白应用,其中所述贻贝粘蛋白浓度为0.1-15.0mg/ml。The mussel mucin application according to claim 1, wherein the mussel mucin concentration is from 0.1 to 15.0 mg/ml. 根据权利要求1的贻贝粘蛋白应用,其中所述贻贝粘蛋白是以液体剂或凝胶剂使用。The mussel mucin application according to claim 1, wherein the mussel mucin is used as a liquid or gel. 根据权利要求1的贻贝粘蛋白应用,其中最终产品中的贻贝粘蛋白是在pH 1.0-7.0的范围内,特别是在pH 3.0-6.5的范围内。The mussel mucin application according to claim 1, wherein the mussel mucin in the final product is in the range of pH 1.0-7.0, particularly in the range of pH 3.0-6.5. 根据实施方式1-5中任一项的贻贝粘蛋白应用,其中所述软组织炎症选自:肌肉、韧带、筋膜、肌腱、滑膜、脂肪、关节囊、淋巴组织的挫伤或裂伤引起的软组织炎症。The mussel mucin application according to any one of embodiments 1 to 5, wherein the soft tissue inflammation is selected from the group consisting of: muscle, ligament, fascia, tendon, synovium, fat, joint capsule, contusion or laceration of lymphoid tissue Soft tissue inflammation. 贻贝粘蛋白作为活性成分在用于治疗软组织炎症的组合物中的应用,其中所述组合物是以液体剂或凝胶剂使用。Use of mussel mucin as an active ingredient in a composition for treating inflammation of a soft tissue, wherein the composition is used as a liquid or gel. 贻贝粘蛋白作为活性成分在用于治疗软组织炎症的药品中的应用。Use of mussel mucin as an active ingredient in medicines for treating soft tissue inflammation. 贻贝粘蛋白作为活性成分在用于治疗软组织炎症的医疗器械中的应用。The use of mussel mucin as an active ingredient in medical devices for treating soft tissue inflammation. 贻贝粘蛋白作为活性成分在用于治疗软组织炎症的保健品或食品中的应用。 The use of mussel mucin as an active ingredient in health care products or foods for treating soft tissue inflammation.
PCT/CN2017/081307 2016-04-20 2017-04-20 Mussel adhesive protein product and use thereof for inhibiting soft tissue inflammation Ceased WO2017181977A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CNPCT/CN2016/079768 2016-04-20
PCT/CN2016/079768 WO2017181373A1 (en) 2016-04-20 2016-04-20 Mussel adhesive protein product and application thereof for suppressing soft-tissue inflammation

Publications (1)

Publication Number Publication Date
WO2017181977A1 true WO2017181977A1 (en) 2017-10-26

Family

ID=60115492

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/CN2016/079768 Ceased WO2017181373A1 (en) 2016-04-20 2016-04-20 Mussel adhesive protein product and application thereof for suppressing soft-tissue inflammation
PCT/CN2017/081307 Ceased WO2017181977A1 (en) 2016-04-20 2017-04-20 Mussel adhesive protein product and use thereof for inhibiting soft tissue inflammation

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/CN2016/079768 Ceased WO2017181373A1 (en) 2016-04-20 2016-04-20 Mussel adhesive protein product and application thereof for suppressing soft-tissue inflammation

Country Status (1)

Country Link
WO (2) WO2017181373A1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW202042813A (en) * 2019-01-10 2020-12-01 大陸商江陰貝瑞森製藥有限公司 New formulations containing leukotriene receptor antagonists
CN115137805A (en) * 2022-07-26 2022-10-04 四川省中医药科学院 Composition with anti-inflammatory, antibacterial and anti-vaginitis effects and application thereof
CN115886244B (en) * 2023-01-05 2024-11-22 南京师范大学 Artificial meat and preparation method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103520766A (en) * 2013-09-25 2014-01-22 高敏 Mussel mucoprotein liquid product as well as preparation method and application thereof
CN105477674A (en) * 2014-10-10 2016-04-13 北京铂铱电气科技有限公司 Hemostasis composite material based on chitosan and marine mussel mucin and preparation method of hemostasis composite material

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103520766A (en) * 2013-09-25 2014-01-22 高敏 Mussel mucoprotein liquid product as well as preparation method and application thereof
CN105477674A (en) * 2014-10-10 2016-04-13 北京铂铱电气科技有限公司 Hemostasis composite material based on chitosan and marine mussel mucin and preparation method of hemostasis composite material

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GAO, MIN ET AL.: "Overview of Mussel Adhesive Proteins", JOURNAL OF ANHUI AGRICULTURAL SCIENCES, vol. 39, no. 32, 30 November 2011 (2011-11-30), pages 19860 - 19862 *
ZHU, YAOYAO ET AL.: "The Research Progress on Mussel Adhesive Proteins", ADVANCES IN MARINE SCIENCE, vol. 32, no. 4, 31 October 2014 (2014-10-31), pages 560 - 570 *

Also Published As

Publication number Publication date
WO2017181373A1 (en) 2017-10-26

Similar Documents

Publication Publication Date Title
JP2002515401A (en) Arginine medication with beneficial effects
CN102223889A (en) Homeopathic treatments
CN105434465B (en) It is a kind of to prevent and treat arthritic pharmaceutical composition and preparation method thereof
WO2017181977A1 (en) Mussel adhesive protein product and use thereof for inhibiting soft tissue inflammation
RU2433844C1 (en) Method of treating degeneratively-dystrophic diseases of musculoskeletal system and posttraumatic pain syndromes
CN104258278A (en) Gushangling (for bone injury) spray
EP2149378B1 (en) Topical formulations for the symptomatic treatment of musculoskeletal disorders
US20030125303A1 (en) Transdermal formulation for repair and maintenance of connective tissue
WO2017181978A1 (en) Mussel adhesive protein product and use of same for inhibiting vascular inflammation
CN106421540A (en) Patch for soft tissue damage and preparation method of patch
WO2017088173A1 (en) Mussel adhesive protein product, and use thereof in suppressing bone inflammation
US20160101141A1 (en) Topical Treatment of Sports Related Injuries
WO2017088177A1 (en) Mussel adhesive protein product, and use thereof in preventing and suppressing neuronal inflammation
CN104873574A (en) Ointment for relieving pain
WO2018161890A1 (en) Application of berberine in preparing drug for treating acute soft tissue injury
CN117357547A (en) Application of pharmaceutical composition in preparation of medicine for treating rheumatoid arthritis
CN119868435B (en) Traditional Chinese medicine composition and traditional Chinese medicine ointment for treating old ankle sprain
Yu et al. Creatine derivatives: rapid complete relief of pain by topical or transcutaneous administration
CN101259138A (en) Anti-inflammatory and analgesic composition for topical application to the parts of the locomotor system of an animal
Souter Sports injuries: treatment guidelines
CN108434299B (en) Pharmaceutical composition for treating scapulohumeral periarthritis and preparation method and spray thereof
RU2241473C2 (en) Gel "stopartros" for prophylaxis and treatment of degenerative-dystrophic injure of articular cartilage and intervertebral disk and method for its preparing
Banning Topical diclofenac: formulations for treating inflammatory pain
CN105456329A (en) Rheumatism pain alleviating medicinal liquor
Souter Sports injuries: treatment guidelines

Legal Events

Date Code Title Description
NENP Non-entry into the national phase

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17785461

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 17785461

Country of ref document: EP

Kind code of ref document: A1